With an annual referral of >150 patients with multiple myeloma (MM) to this center, support is requested to establish a MYELOMA DATA BANK and conduct THERAPEUTIC RESEARCH. The MM Data Bank will capture parameters likely to contribute to further understanding of disease etiology, clinical heterogeneity and progression and will emphasize cytogenetics, oncogenes and tumor suppressor genes, cytokines and tumor phenotypic characteristics and immune status; in addition to prognostic parameters of tumor burden and cell kinetics. These biologic parameters will also be evaluated in relationship to race (increased incidence of MM among Blacks), occupational exposure, family history of cancer particularly B cell malignancies, and patient age. In newly diagnosed MM, a "Total Therapy" program will examine whether remission induction with mutually non-cross resistant regimens followed by double autologous transplantation (DAT) with high dose melphalan (MEL-200) and subsequent interferon (IFN)-alpha maintenance will effect a high frequency of true complete remission (CR). A high CR rate of about 50% is expected to translate into marked extension of progression-free survival and possibly cure in some patients. In previously treated patients, DAT will be further developed (MEL-200 followed by MEL + TBI); gene transfer technology will be used to trace the nature of relapse; and biological agents will be evaluated, such as IFN-beta-1, IL-4, and all-trans- retinoic acid (ATRA), which may exert their clinical effects by interfering with the cytokine network involved in MM growth and differentiation. Patients with advanced disease will be candidates for MEL with GM-CSF and added IL-3, to determine the maximum tolerated dose (MTD) of IL-3 and subsequently the MTD of MEL that can be administered without hemopoietic stem cell support. Collectively, the proposed studies should advance the understanding of the genetic abnormalities involved in abnormal cytokine production and point to new avenues of therapeutic intervention by biological agents. The Total Therapy program will test whether currently available therapy, used in maximum dose intensity, can bring about long term disease control and cure in a subset of patients to be defined on the basis of the MM Data Bank.